Now Playing at a Nearby Lab: 'Revenge of the Fly People'

By NICHOLAS WADE

Published: May 20, 1997

The quirky names, each carefully annotated, can be found on a Web site known as Flybase, the compendium of knowledge and home page of the world's 5,600 fly people. It is a point of honor among fly people, as biologists who study the laboratory fruit fly call themselves, to avoid giving unimaginative names to the new genes they identify in their favorite organism.

The fruit fly is a little speck of a thing, most noticeable in the form of the hovering clouds that emerge from that forgotten peach at the bottom of the fruit bowl. But this little speck has now become the center of a vast research enterprise, the focus of attention of many of the world's best biologists.

Their goal is to take the fly apart and put it back together by thorough analysis of its genes. When they can do that, they hope to understand several of life's deepest mysteries, like how a complex organism develops from a simple egg and how a nervous system is wired to produce a certain pattern of behavior.

Medical research agencies willingly support fruit fly research because its relevance to humans has turned out to be surprisingly direct. Many of the most important fruit fly genes, like those that tell the developing embryo to produce organs in certain places, have been found to have counterparts in humans. The fly and human versions of these genes are not identical but have recognizably similar DNA sequences, reflecting their descent from a common ancestral gene some 600 million years ago.

Fly people are now positioned on the forefront of biological research. Since their organism is so easy to study, many significant genes are discovered first in flies, allowing other researchers to find counterparts in mice or men. The fly people's penchant for playful gene names has tended to cross over, too. A gene called fringe in the fruit fly has vertebrate counterparts named manic, lunatic and radical.

The fly's present pre-eminence in biology comes after a series of ups and downs. The Drosophila fruit fly was first chosen for scientific study in 1908 by Thomas Hunt Morgan of Columbia University. Morgan and his pupils worked out much of what is now standard genetics on the fruit fly. But Drosophila took a back seat after the discovery of DNA in 1953. The pioneers of modern molecular biology did their work in viruses and bacteria, the simplest forms of life. Fruit fly research stagnated.

The fly flew back into prominence when biologists skilled in the techniques developed for studying viruses and bacteria decided to tackle the far more complicated cells of higher organisms, and chose Drosophila as their vehicle. Several genetic techniques were developed in the fruit fly bv Dr. David Hogness of Stanford University, and by students of his such as Dr. Gerald M. Rubin of the University of California, Berkeley.

By the 1980's, spectacular discoveries began to emerge about the genes that govern development of the early embryo. Some of these processes were special to insects, but the master genes that controlled them seemed to be part of a general plan for patterning all animal bodies.

Until the discovery of the patterning genes, said Dr. Ralph J. Greenspan of New York University, ''it was very difficult to gain acceptance in other fields because they thought flies were irrelevant.''

''Gene homology with humans really legitimized the fly,'' Dr. Greenspan said of the similarities in the genes' DNA sequences. Drosophila researchers who had sought Federal grants on the grounds that their work would be relevant to humans found their arguments were even truer than they had thought, Dr. Rubin noted.

But at their moment of triumph, the fly people were threatened by rival tribes of biologists seeking knowledge from other totem animals. Some favored a tiny transparent worm, known as C. elegans. One of the fly people's stars, Dr. Christiane Nusslein-Volhard, now of the Max Planck Institute in Tubingen, Germany, began development of another model organism, the zebra fish of tropical aquariums. A technique for deleting genes put the mouse on the map as a workable model.

The National Institutes of Health supports research on all these animals as part of its human genome project, to which it deems each will contribute. For a time it seemed that creatures with backbones would provide a surer guide to human genetics. But the fly people have fended off their rivals, at least for the moment, saved by the surprising and extensive overlap of the genes among all the model organisms, and because the techniques for manipulating the fly's genetics are so much further advanced.

Drosophila research is now flourishing as never before. In the late 1980's about 200 researchers attended the annual national fly meeting. At last month's meeting in Chicago, some 1,400 people showed up. Dr. Kathy A. Matthews of Indiana University keeps the Fort Knox of the fly world, a collection of some 4,500 different strains of Drosophila maintained at the stock center at Bloomington. She sends out some 600 shipments every week to fly laboratories, a quarter of them outside the United States.

''The field has been growing every year for the 10 years I have been here,'' Dr. Matthews said. ''We have been growing by 20 to 30 percent a year.''